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We investigated selected oxylipins and related synthesizing/signaling pathways in 28 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and 39 controls. Plasma and mucosal PUFA/oxylipin profiles were analyzed by LC-MS/MS. mRNA expression of 5, 12 and 15-lipooxygenases, FPR2/ALXR, FFAR4/GPR120, annexin A1, and interleukin-10 were analyzed by qRT-PCR. Oxylipin profile and related metabolic pathways were altered in both CD and UC patients. The patterns were characterized by increased prostaglandins, leukotrienes, and lipoxins and overexpression of 5-lipoxygenase, FPR2/ALXR, annexin A1, and interleukin-10 genes, but decreased n-3 PUFAs and 18-hydroxyeisapentaenoic acid. The gene of 15-lipoxygenase was under-expressed mainly in UC patients. CD and UC are associated with unbalanced n-6 ​​and n-3 derivatives and pro-inflammatory and anti-inflammatory/pro-resolving mediators favoring the former compounds. The findings suggest that oxylipins engage in the pathophysiology of the diseases. Targeting oxylipin's metabolic pathways would be a promising therapy for inflammatory bowel diseases., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Selected mucosal and plasma polyunsaturated fatty acids (PUFAs) and related oxylipins and endocannabinoids were determined in 28 Crohn's disease (CD) patients and 39 controls. Fasting blood and colonic biopsies were collected in all participants, during a disease flare for the patients. Thirty-two lipid mediators including PUFAs, oxylipins, and endocannabinoids were assessed by LC-MS/MS. The pattern of lipid mediators in CD patients is characterized by an increase in arachidonic acid-derived oxylipins and endocannabinoids and a decrease in n-3 PUFAs and related endocannabinoids. A model combining increased 6-epi-lipoxin A4 and 2-arachidonyl glycerol with decreased docoasapentaenoic acid in plasma fairly discriminates patients from controls and may represent a lipidomic signature for CD flare. The study findings suggest that lipid mediators are involved in CD pathophysiology and may serve as biomarkers for disease flare. Further research is required to confirm the role of these bioactive lipids and test their therapeutic potential in CD., Competing Interests: Conflicts of interests The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Anti-TNFα associated to seton drainage has a central role in the treatment of complex perineal Crohn's fistulas (PAF). A precise treatment protocol is lacking., Aims: to evaluate the results of this combined treatment and identify predictive factors of response., Methods: It was a retrospective study which included all patients with complex PAF treated with Anti-TNFα., Results: We included 49 patients, mean age of 31.6 years. 17 patients had an active rectal involvement. 35 patients had azathioprin. After the induction, 43 patients had a clinical response. Maintenance therapy was started in 45 cases. After a median of 19 months of Anti-TNFα, 24 patients had a clinical remission (with radiological remission in 20), 17 a partial clinical response, and 4 were in failure. After clinico-radiologic remission setons were removed in all patients, 46% of patients who stopped Anti-TNFα treatment after clinico-radiologic remission relapsed. Absence of rectal involvement and Clinical remission after induction were the independent predictive factors of achieving a clinical remission under maintenance therapy with Anti-TNFα (p=0.016) and clinico-radiological remission (p=0.028)., Conclusion: An Anti-TNFα based treatment combined with long term loose seton drainage have contributed to the high rates of both clinical and radiological responses in this study. Obtaining a "deep" clinico-radiological remission should be the target of the treatment. Stopping the Anti-TNFα should be avoided even after obtaining such response.

Background - Crohn's disease is a clinically heterogeneous condition. Our aim was to identify the phenotype evolution of Crohn's disease over time according to the Montreal Classification and to precise predictive factors of the need for immunosuppressant treatment or surgery. Methods - We included Crohn's disease patients who were followed up for at least 5 years. We excluded patients who were lost to follow up before five. Patients were classified according to the Montreal classification for phenotype at diagnosis and five years later. The evolution of phenotype over time and the need for surgery, immunosuppressive or immunomodulatory drugs were evaluated. Results - One hundred twenty consecutive patients were recruited: 70 males and 50 females. At diagnosis, 68% of patients belong to A2 as determined by the Montreal classification. Disease was most often localized in the colon. The disease location in Crohn's disease remains relatively stable over time, with 93.4% of patients showing no change in disease location. Crohn's disease phenotype changed during follow up, with an increase in stricturing and penetrating phenotypes from 6% to 11% after 5 years. The only predictive factor of phenotype change was the small bowel involvement (OR=3.7 [1.2-7.6]). During follow-up, 82% of patients have presented a severe disease as attested by the use of immunosuppressive drugs or surgery. The factors associated with the disease severity were: small bowel involvement (L1), the stricturing (B2) and penetrating (B3) phenotypes and perineal lesions (OR=17.3 [8.4-19.7]; 12 [7.6-17.2]; 3[1.7-8.3] and 2.8 [2.2-5.1] respectively), without association with age, sex or smoking habits. Conclusion - Crohn's disease evolves over time: inflammatory diseases progress to more aggressive stricturing and penetrating phenotypes. The ileal location, the stricturing and penetrating forms and perineal lesions were predictive of surgery and immunosuppressant or immunomodulatory treatment.

Introudction Crohn's disease (CD) is a lifelong condition. Multiple imaging investigations are often performed during follow-up. This could cause overexposure to radiation. The aim of our study was to determine mean radiation dose in patients  with  at least a 5-year course of CD and to determine possible risk factors associated with exposure to high doses of radiation. Methods We conducted a retrospective study including patients whose CD was diagnosed between 1998 and 2005. Epidemiologic features of patients, characteristics of the disease,  types of imaging investigations that were performed during follow-up and cumulative radiation effective dose were determined. Risk factors associated with exposure to high doses of radiation were then determined. Results One hundred sixty seven patients were included.  There were 92 males (55.1%) and 75 females (44.9%) with mean age at dianosis of 31.4±12.3years. Global radiation dose was 18.8±18.9 mSv. Twenty seven patients (16,2%) were exposed to more than  35 mSv and 4 patients (2.4%) had an exposure  of more than  75 mSv. Use of Infliximab, age at disease onset ≤ 24 years old and number of flares ≥ 8  were independent risk factors of radiation exposure more than 35 mSv with adjusted Odds ratios (OR) : 2.5 [2.1- 5.3]; 1.6 [1.2- 4.7] and 3.2 [2.1- 7.8] respectively. Similarly,  use of Infliximab and number of flares ≥ 8  were independent risk factors of radiation exposure more than 75 mSv with adjusted OR : 4.3 [2.8-9.5] and 7 [3.2-11.2] respectively. Conclusion Radiation risk seems to be increased with severe course of  CD. Both referring physicians and radiologists have the responsibility to minimise radiation exposure. Entero-magnetic resonance imaging (Entero-MRI)  may reduce this risk.

Background: Crohn's disease is a chronic relapsing- remitting affection. It has a strong immunologic component which represent the target of standard therapies including immunosppressants and biological therapies. However, many patients remain refracory or intolerant to these therapies., Aim: The aim of this review is to determine the effects of stem cell transplantation in patients with refractory Crohn's disease., Methods: Systematic review of observational studies, clinical trials and case reports that focused on the effectiveness and safety of stem cell transplantation in patients with refractory Crohn's disease., Results: Hematopoietic stem cell transplantation seems to be efficient in maintaining clinical and endoscopic remission in patients with Crohn's disease refractory or intolerant to current therapies. However, it has been associated to high morbidity and mortality due to chemotherapy. Mesenchymal stem cell transplantation could induce remission in patients with fistulising refractory Crohns disease with no severe side effects. Its impact on luminal Crohns disease is still controversial., Conclusion: Stem cell transplantation seems to hold promising in patients with refractory Crohn's disease. However, because of the high morbidity and mortality related to chemotherapy, hematopoietic stem cell transplantation should be used as last resort to control this disease. Effectiveness of mesenchymal stem cell transplantation in luminal Crohn's disease has yet to be proven.

Background: Diet is thought to have an important role in the etiopathogenesis of Crohn's disease. In the other hand, Crohn's disease is frequently associated with nutritional deficiencies probably as result of disease activity and poor oral intake., Aims: To investigate the dietary intake in patients with Crohn's disease in comparison with matched population controls and to assess the correlation between the results of the dietary enquete, nutritional status and disease activity., Methods: We conducted a prospective case control study in patients with Crohn's disease and matched controls. All subjects were evaluated in respect of dietary intake (based on "NUTISTAR" logiciel) and nutritional status., Results: We studied 23 patients and 23 controls. There was no statistical difference between patients and controls according to the proportion of carbohydrates, fat and protein intakes. Energy intakes were significantly lower in patients with Crohn's disease (1991 + 678 kcal/j) compared to controls (2537 + 345 kcal/j) (p=0.007) ; and in active disease (1353 + 308 kcal/j) compared to inactive disease patients (2481 + 415 kcal/j) (p<0.0001). In Crohn's disease patients, correlation study showed that energy intakes were correlated with CDAI (p<0.0001 ; r = - 0.74) and BMI (p=0.03 ; r = 0.45)., Conclusion: In Crohn's disease, an inadequate dietary intake is correlated with nutritional status and disease activity.

Background: The natural history of Crohn's disease is associated with several factors that affect the prognostic of the patients., Aims: To determine the most prognostic factors in Crohn's disease, based on a systematic review., Methods: Literature review., Results: The most important factors to consider in patients with Crohn's disease are the need for immunosuppressive therapy, the need for intestinal resection and disabling disease. Prognostic factors for these events are ileal involvement, perianal disease and initial treatment by corticosteroid. Other factors such young age, CRP level and smoking status, has not been found in all population-based studies. Protective role of anti-TNF drugs is strongly suggested but need to be confirmed in further studies., Conclusion: In a selected subgroup of patients with Crohn's disease characterized by the presence of these prognostic markers, the "topdown" strategy can be proposed.

Background: Adalimumab is the first subcutaneously self administered fully human anti-TNFa., Aim: To determine efficacy and safety of Adalimumab therapy in Crohn disease., Methods: Literature review., Results: Adalimumab has been evaluated for its effect in inducing and maintaining remission and its steroid-sparing effect of refractory Crohn's disease. In addition, it offers a significant treatment option in patients who have lost response to or become intolerant to Infliximab. Results also suggest efficacy of Adalimumab in fistulising Crohn's disease but more studies are needed. Adalimumab was well tolerated and studies show that all anti-TNF inhibitors have similar safety profiles.

Background: Immunosupressors, particularly azathioprine, represents the therapeutic alternative in patients with corticodependant or corticoresistant Crohn's disease. The prescription of azathioprine in Tunisia is common, but there is not Tunisian studies evaluating the long term results of this drug in Crohn's disease patients., Aims: To evaluate the long term results of azathioprine treatment with determination of rates of relapses, surgery and need to corticosteroids in patients with corticodependant or corticoresistant Crohn's disease, and to look for predictive factors to theses events., Methods: A retrospective study on 12 years including all patients treated by azathioprine for corticodependant or corticoresistant Crohn's disease. We excluded the cases of follow up less than 6 months., Results: We studied 56 patients (46 corticodependant and 10 corticoresistant). Induction of remission was obtained in 89% of the cases. Concerning the long term results, the relapse rate was 60% of patients treated with azathioprine, with actuarial rates of 38% at one year, 65% at 5 years and 75% at 10 years. Need for corticosteroid treatment was estimated at 42% and need for surgical treatment was estimated at 24%. The only predictive factor for relapse was duration of treatment by azathioprine more than 36 months, with sensitivity of 93% and specificity of 50%., Conclusion: Although an excellent result of azathioprine in induction remission, long term results showed deterioration of results of treatment. Physicians must be followed up Crohn's disease patients in order to rapidly detect and treat the clinical relapses of the disease.

Background: Small-bowel videocapsule endoscopy (VCE) is a new technique in evaluation of intestinal involvement in several pathologies. Crohn's disease affects principally terminal ileum. Small bowel involvement in Crohn's disease is not well estimated by endoscopic and radiologic conventional techniques., Aims: To evaluate the performances of VCE in detection of asymptomatic proximal small bowel lesions in consecutive patients with Crohn's disease with terminal ileal involvement, to compare the results of VCE to small bowel radiography and CT-enteroclysis and to determine the therapeutic impact of VCE in these patients., Methods: A prospective study which included Crohn's disease patients with distal ileal involvement, based on radiological or endoscopic findings. We performed in all patients small bowel radiography, CT enteroclysis and VCE. Proximal involvement was characterized by presence of aphtoid, superficial or deep ulcerations in the jejunum or the proximal ileum., Results: We studied 20 patients (12 men, mean age 31.6 years). VCE confirmed the distal ileal involvement in all patients. Significative proximal lesions was observed in nine patients (jejunum only: one case, jejunum and ileum: six cases and proximal ileum: two cases), in most cases aphtoid or superficial lesions. Deep ulcerations were observed in two patients. Small bowel radiography showed proximal ileal lesions in only two patients, and CT-enteroclysis in only one patient. Treatment by azathioprine was prescribed in two patients with severe and extended small bowel lesions in VCE examination., Conclusion: VCE is more accurate than radiologic techniques in detection of small bowel lesions in Crohn's disease. In cases of severe and extended small bowel involvement, VCE can conduct to changes of therapeutic approach.

Background: Evaluation of activity of Crohn's disease is based on CDAI. Several other tools have been studied to assess disease activity with more accuracy., Aims: To assess the correlation between Doppler parameters of superior mesenteric artery and disease activity and to assess the accuracy of these parameters in discriminating between active and quiescent Crohn's disease., Material and Methods: We perform a prospective study including non-operated and non-complicated Crohn's disease patients involving terminal ileum and/or right colon and sex and age-matched controls. Doppler sonography of superior mesenteric artery was performed in all subjects., Results: We studied 41 patients and 15 controls. There was no statistical difference between patients and controls according to the studied US parameters. The difference in resistance index between the three groups using analysis of variance is not significant (p=0.064). Resistance index was significantly lower in patients with active disease compared to inactive disease patients (0.82 +/- 0.04 vs 0.85 +/- 0.03; p=0.01). Pulsatility index was also lower in patients with active disease compared to inactive disease patients (1.37 +/- 0.21 vs 1.53 +/- 0.15; p=0.01). A value of resistance index less than 0.79 predicted active disease with a sensitivity of 35.3% and specificity of 95.7%. A value of pulsatility index less than 1.56 predicted active disease with a sensitivity of 94.1% and specificity of 43.5%. In case of resistance index less than 0.79 and pulsatility index less than 1.56 in the same patient, the probability of active disease was 86%. However, in case of resistance index over than 0.79 and pulsatility index over than 1.56, this probability was only 9%. In Crohn's disease patients, correlation study showed that resistance index value was significantly correlated with CDAI (r=-0.46; p=0.003). Pulsatility index value was also correlated with CDAI (r=-0.39; p=0.01)., Conclusion: Doppler sonographic parameters of superior mesenteric artery are significantly correlated with disease activity in non-operated and non-complicated Crohn's disease., (Copyright © 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background/aims: Azathioprine is the most commonly used immunomodulator in Crohn's disease. The aims of the study are to determine the cumulative frequency of azathioprine prescription in non selected consecutive inpatients with Crohn's disease and to identify a subgroup of patients with high risk of azathioprine prescription during the follow-up., Methodology: We studied consecutive in patients with established diagnosis of Crohn's disease admitted in our department in years 2002 and 2003. Cumulative frequency of azathioprine use during the follow-up was calculated. Predictive factors of azathioprine use were studies based on clinical, biological and endoscopic charts at the first hospitalization in our department., Results: We include 88 patients (52 males, mean age 31.3 years (18 - 68)). Azathioprine was prescribed in 38 patients (43.2%) with a mean period of 12.9 months (1 - 90) after the first hospitalization. The cumulative frequency of azathioprine prescription was 11% the first month, 31% at 6 months, 35% at one year and 49% at 6 years. In univariate analysis, azathioprine use was more frequent in previously treated patients in an other department (p = 0.05), in case of ileal involvement > 40 cm (p = 0.02), previously treated patients with corticosteroids (p = 0.001), first treatment in our unit by corticosteroids (p < 0.0001), duration of the flare more than 6 months (p = 0.01), CDAI > 204 points (p < 0.0001), Hemoglobin level < 9.7 g/ dl (p < 0.0001) and cholesterolemia level < 1.32 g/l (p < 0.0001). Independent factors associated with azathioprine use in our population were diffuse involvement of the ileum at initial hospitalization (p = 0.0001; OR [95%CI]: 17.9 [4.1-77.9]), and previous prescription of corticosteroid therapy (p = 0.04; OR [95% CI]: 5 [1.1-25])., Conclusion: Azathioprine is frequently used in adult Crohn's disease patients, maximally within the first year after the first hospitalization. Patients with diffuse ileal involvement and previously treated patients with corticosteroids are at higher risk to azathioprine use and should have systematically the preventive strategies to ovoid opportunistic infections since their first visit.

Background: Infliximab has been an effective chimerical monoclonal antibody in Crohn's disease. Infliximab is available in Tunisia for a few years., Aims: To determine the results of the treatment of Crohn's disease by infliximab., Methods: We undertook a retrospective study relating to all the Crohn's disease patients and treated by infliximab. For all the patients, we specified the indication of the treatment, the result of the induction treatment, the recourse or not to a sequential treatment and the adverse effects of the treatment., Results: Our study related to 20 patients. It was in the majority of the cases an anoperineal and fistulizing form (15 case). Good response to the induction treatment was noted in 15 patients (75%). A sequential treatment by infliximab was undertaken among seven patients, with good results in the short and medium term. A case of death related to the treatment was noted in our series, as mortal milliary tuberculosis appeared under treatment., Conclusion: Infliximab must be reserved for particular situations of the Crohn's disease. The pre-therapeutic assessment must be complete and the monitoring of the patients must be strict, while insisting on the possibility of reactivation of latent tuberculosis in Tunisia.

Background: Inflammatory bowel diseases are frequently associated with extra-intestinal manifestations and other autoimmune disorders. Association between primary sclerosing cholangitis and Crohn's disease is established. However, the association of antiphospholipid syndrome with Crohn's disease was reported in the literature only in the form of isolated case reports., Aims: To report a Tunisian case of association of Crohn's disease, primary sclerosing cholangitis and antiphospholipid syndrome., Case Report: We report the case of a patient presenting a colonic Crohn's disease associated with primary sclerosing cholangitis and antiphospholipid syndrome. Sclerosing cholangitis was diagnosed basing on disturbances of the hepatic biochemical tests. Antiphospholipid syndrome was revealed by a venous thrombosis of the lower limbs., Conclusion: Although the anticardiolipin antibodies were frequently found during the course of primary sclerosing cholangitis, the association with antiphospholipid syndrome is exceptionally described. In the same way, triple association of primary sclerosing cholangitis, Crohn's disease and antiphospholipid syndrome was not brought back in the literature.

Aims: To determine the factors associated with an increased C-reactive protein level in Crohn's disease patients and to seek a correlation between the C-reactive protein value and the Crohn's disease activity index., Methods: We prospectively studied 103 Crohn's disease patients, 76% of whose disease was active at the time of inclusion. C-reactive protein measurement was carried out on all patients. An increased C-reactive protein level was defined as >/=10mg/L., Results: The median C-reactive protein rate was 53.9mg/L (ranging from 1 to 228mg/L). An increased C-reactive protein was found in 77 patients (75%). By univariate analysis, ileocolic localization, severity of the flare, erythrocyte sedimentation rate, leukocyte and platelet count, fibrinogen, albumin, serum calcium and Crohn's disease activity index were found to be associated to elevated C-reactive protein values. By multivariate analysis, independent factors associated with an increased C-reactive protein level were: ileocolic localization (p=0.02; OR [95% CI]: 2.84 [1.25-9.52]) and moderate or severe disease activity (p=0.001; OR [95% CI]: 4.20 [1.92-8.64]). A statistically significant association between the Crohn's disease activity index score and the C-reactive protein level was found in our study (r=0.302; p=0.001). The optimal C-reactive protein threshold value that separates patients with moderate to severe disease (Crohn's disease activity index>220) from the others was calculated to be 19mg/L with a sensitivity of 76.4% and a specificity of 56.2%., Conclusion: The C-reactive protein level is correlated to disease activity in Crohn's disease. Its role seems to be essential in predicting moderate and severe disease activity.